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January 26, 2006
Issues of the Heart
For the last five years, PPMD has been providing support and promoting the need for cardiac consensus. Thankfully, the notion of early diagnosis, early intervention with the goal of prevention or delaying the onset of dilated cardiomyopathy in DMD is now at the forefront and driving down the road toward “Standards”. This is again where patients and family members have made all the difference, insisting on baseline studies (echocardiogram and Cardiac MRI) and inquiring about early treatment. It is easy enough to say, at a certain age all boys should be taking ace inhibitors and physicians should consider adding beta blockers BUT (and there is always a but) physicians are often reluctant because intervention must be based on evidence and physicians disagree on what constitutes ‘evidence’. Herein is the dilemma and it is especially difficult in rare disease.
Often families approach their physicians with a single article in hand that describes improvements in a small number of individuals in a short term study. Often physicians respond negatively to such information. I am sure we could develop a list of reasons why this is the case but there are fundamental issues that we also need to understand.
Evidence in rare disease is a major issue. Questions such as how much benefit in how many individuals and over what period of time, how credible is the source, how strict was the investigation (clinical trial) and how good is the data.
Evidence-based information is always a product of a systematic, evidence-based process. Differences in the process are related mainly to the rigidity of the criteria and how high you place the bar. The difficulty of all this in rare conditions such as DMD is twofold:
• if the bar is too low, safety may be compromised.
• if the bar is too high, access to potentially useful treatments could be lost.
Physicians are faced with this dilemma every day– how many patients were treated, for how long and with how much benefit? As you might imagine, there are many other layers as well, which include credibility of the journal that published the information, credibility of the authors, individual philosophy, education, experience and on and on.
In matters of the HEART - we are aggressively working through these issues. Linda Cripe at Cincinnati Childrens’ Hospital Medical Center is working with leading DMD centers (Children’s Hospital of Philadelphia, University of Iowa, University of Utah) to make sure our children’s hearts have the best of care. Thankfully, MDA is now onboard and agreed to disseminate the information as well.
Posted by ppmd at 11:55 AM | Comments (0)
January 11, 2006
January 2006
Last year ended on a very high note. Two boys received PTC124 at Children’s Hospital of Philadelphia, often referred to as CHOP. Since that time, Cincinnati Children’s Hospital has started the PTC124 trial. Each center begins the trial by dosing 2 boys with PTC 124. For a short period following this initiation, the boys will be evaluated and have blood drawn for laboratory studies. This is done for safety reasons, to identify any side effects that may result from the drug. Once this initial period is complete, each site will add additional boys until there are a total of 10 boys at each site. The Utah site is expected to begin in the next couple of weeks. To say we are all hopeful is a misnomer. We are thrilled, anxious, biting our nails and tremendously positive! This trial, while specific for boys with premature stop codons, is a milestone for all of us. This will be the first time in history that dystrophin is restored in muscle. The information gained from this trial will benefit everyone, the entire DMD community. It will create a paradigm shift, a shift in philosophy. If it works (and we are praying it will), a certain subset of boys with DMD will have treatment. It will proclaim that Duchenne, once considered ‘hopeless and untreatable’ is neither hopeless nor untreatable. It will be a magnificent step forward for all of us.
On December 29, PPMD and PTC Therapeutics officially entered the Optimization phase of our drug development. You may remember in 2003, we started Project Catalyst. This was the beginning of our work with PTC Therapeutics. PTC performed high throughput screens on 5 targets with the goal of developing treatments that would apply to ALL individuals diagnosed with DMD. We have hits on all targets and have initiated the Optimization phase – the process of validating those hits and performing initial testing for toxicity. This phase is expected to be complete in April. At that time, we expect to have specific compounds that could potentially be formulated into small molecules for clinical trial.
The first weekend of January, we left for Florida. PPMD participated in the Disney Marathon. 125 runners! Inspiring! Remarkable! Wonderful! Saturday was the half marathon and Sunday, the full marathon. Several of our runners ran both! It is true, the marathon is a test of endurance and strength, but it was something much more. It was something that was very hard to put into words. This marathon was a demonstration of a community willing to do anything it takes to help their children, all of our children. Kim and I planted ourselves in the Magic Kingdom. For the half marathon, this was the 8-mile mark and for the full marathon, it was the 10-mile mark. We stood on Main Street with full view of every runner. It was thrilling to see fathers, mothers, friends, and relatives coming around that bend, wearing the PPMD lime green singlets. We were in tears much of the time. The strength and determination of those runners, the willingness to FACE IT, LIVE IT and CHANGE IT for all of our sons, for all of us, was more than empowering. As some of the runners passed, they would stretch out their hands for a ‘high five’. I felt their power, their desire to make things different and I knew that we can, and we will, change the face of DMD forever. This is our second year participating and these runners generated over $300,000. It was an inspiration to see family and friends all running against time. One runner had a small round photo of a young boy on his shirt and the words 'in memory'. As he passed me, he raised his hand for a 'high five' and I knew he was running for our boys as well.
Last year, we initiated a collaborative effort on exon skipping. We believe the antisense oligonucleotides are very promising as a potential treatment for DMD. To this end, we thought it essential to create a business model that would accelerate translation. I’m happy to say the consortium is up and running. The formal announcement will be this weekend. I will provide details next week.
Wishing all of you a Happy, Healthy, New Year full of HOPE.
Posted by ppmd at 03:45 PM | Comments (0)